Design and development of a Bayesian risk assessment model for bacterial infection (BRAIN) in patients admitted to hospital from ED.

Streptococcus pneumoniae (Sp) is the leading bacterial pathogen causing complicated pneumonia, that is, with parapneumonic effusion/pleural empyema (PPE/PE). In 2022, there was a rise in group A Streptococcus (GAS)-complicated pneumonias in children. We reviewed the clinical characteristics of Sp- or GAS-complicated pneumonias admitted to 4 Portuguese tertiary hospitals, in 2018-2023. Of the 128 cases, 107 were by Sp and 21 by GAS, with a rise in PPE/PE in 2023. Pathogens were identified by molecular methods (89.8%) or culture (16.4%) from pleural fluid or blood. The mean age was 3.8 years (standard deviation 2.9) and 52.3% were male. Children with GAS PPE/PE were more likely to have rash (57.1% vs. 3.8%, P < 0.001), pharyngitis (52.4% vs. 19.8%, P = 0.004), septic shock (28.6% vs. 0.9%, p <0.001), higher procalcitonin (PCT) (80 vs. 2.13 ng/mL, P = 0.005), higher rates of admission to the intensive care unit (81.0% vs. 55.1%, P = 0.030) and of invasive mechanical ventilation (38.1% vs. 11.2%, P = 0.005). Fatality rate was similar in both groups (4.8% vs. 0%, P = 0.164). Among cases where genotyping was possible, 4/7 GAS were emm 1 (3/4 M1 UK sublineage, all in 2023) and 64/88 Sp were serotype 3. Sp serotype 3 remains the leading cause of PPE/PE in children in Portugal. The increase in GAS PPE/PE cases in 2023 followed an expansion of the M1 UK sublineage in Portugal. GAS should be considered, especially in children presenting with rash, pharyngitis or higher PCT levels. Adequate antimicrobial and clinical management of GAS PPE/PE could be crucial to improve outcomes.

Urosepsis is a severe complication of urinary tract infection (UTI) and may lead to organ dysfunction and death. Early identification remains challenging at initial presentation, highlighting the need for improved risk stratification using routinely available data. This single-center retrospective study analyzed clinical data from 182 hospitalized patients with culture-confirmed UTI, including 89 with culture-defined bacteremic urosepsis (concurrent positive blood and urine cultures) and 93 with non-bacteremic UTI. Random Forest (RF), Extreme Gradient Boosting (XGBoost), and multivariable logistic regression (LR) models were developed using routine biomarkers obtained within 0-24h of the index time; outcomes were assigned using culture results within 48-72h to minimize information leakage. Discrimination was assessed using the area under the receiver operating characteristic curve (AUC) with bootstrap 95% confidence interval (CI) on a held-out test set. D-dimer was consistently ranked among the top predictors. Compared with non-bacteremic UTI, bacteremic urosepsis showed higher procalcitonin (PCT), C-reactive protein (CRP), and white blood cell count (WBC) and lower albumin (all p < 0.05). On the held-out test set (n = 37; positives = 18), XGBoost achieved an AUC of 0.886 (95% CI 0.763-0.971), compared with 0.822 (95% CI 0.665-0.938) for RF and 0.822 (95% CI 0.663-0.935) for LR; the AUC difference between XGBoost and RF was not statistically significant (DeLong p = 0.072). Using routine biomarkers available within 24h, RF and XGBoost demonstrated good discrimination for culture-defined bacteremic urosepsis among inpatients with culture-confirmed UTI. XGBoost yielded a numerically higher AUC than RF, but the difference was not statistically significant in this modest test set. D-dimer, procalcitonin, and albumin emerged as key predictors, supporting the potential utility of routine laboratory indicators for early risk stratification pending external validation.

Background: Multiple organ dysfunction syndrome (MODS) remains a predominant cause of mortality in Pediatric Intensive Care Units (PICUs). While the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score is the established standard for assessing severity, it requires time-consuming serial calculations. There is an urgent need for a rapid, admission-based prognostic biomarker. This study evaluates the association between serum procalcitonin (PCT) and the severity of organ dysfunction in critically ill children. Methods: A prospective cross-sectional study was conducted at Dr. Moewardi Regional General Hospital, Indonesia, involving 25 children aged 1 month to 18 years with suspected infection. Organ dysfunction was quantified using the PELOD-2 score, and serum PCT was measured via Enzyme-Linked Fluorescent Assay (ELFA) within 24 hours of admission. Statistical analysis utilized Spearman’s rank correlation, multivariate linear regression, and Receiver Operating Characteristic (ROC) curve analysis. Results: The cohort had a median age of 12 months. The median PCT level was 0.88 ng/mL. A significant positive correlation was observed between serum PCT and PELOD-2 scores (r = 0.39, p = 0.051; multivariate beta = 0.42, p = 0.043). ROC analysis identified a PCT threshold of greater than 11 ng/mL as the optimal indicator for moderate-to-severe organ dysfunction (AUC 0.82). Patients exceeding this threshold had a significantly elevated risk (Risk Ratio = 2.20; 95 percent CI: 1.15–4.24; p = 0.035). Conclusion: Early serum procalcitonin measurement serves as a powerful independent factor associated with organ dysfunction severity. A cutoff value of greater than 11 ng/mL significantly stratifies risk, allowing clinicians to anticipate the progression of organ failure.

Antibiotic stewardship is becoming increasingly important in neonatal care. This is particularly the case for managing early-onset sepsis (EOS), given the impact on hospitalization, short- and long-term health, and antibiotic resistance. Despite the available evidence supporting various antibiotic stewardship interventions to reduce antibiotic use, evidence regarding their implementation remains limited. This study aimed to identify barriers and facilitators of implementing three evidence-based antibiotic stewardship interventions in EOS care: the EOS calculator, procalcitonin (PCT)-guided therapy, and IV-to-oral switch therapy. Eleven semi-structured focus group interviews were conducted with 81 participants, including pediatricians, neonatal nurses, pediatric residents, midwives, primary care maternity nurses, microbiologists, pharmacists, and general practitioners. The Consolidated Framework for Implementation Research (CFIR), with its five domains (intervention characteristics, outer setting, inner setting, individual characteristics, and implementation process), was used for data collection and analysis. A rapid deductive content analysis approach was used. The interviews identified 34 barriers, mostly found in the inner setting (n = 11), intervention characteristics (n = 10), and the individual health professional level (n = 8). Twenty facilitators were identified, mostly related to intervention characteristics (n = 8). The overarching barriers were identified as external pressure to adhere to the national guidelines and the expected shift in care responsibility. Facilitators identified unanimously by all participants included universal dissatisfaction with the current national guidelines, a hospital culture of evidence-based and patient-centered care, and the presence of a strong opinion leader. Implementation strategies should address these barriers and facilitators, seeking to balance quality of evidence with professional core values, managing shifts in care, enhancing interdisciplinary communication, and reducing practice variation by addressing dissatisfaction with un-updated guidelines at an earlier stage.

Sepsis and septic shock stimulate a massive inflammatory response during which neutrophil extracellular traps (NETs) release citrullinated histone H3 (CitH3) into the circulation, leading to tissue damage, coagulopathy, and organ failure. This study aimed to assess serum levels of CitH3 in patients with septic and non-septic shock in intensive care units and to study their correlation to septic shock severity. The study was conducted at Ain Shams University Hospitals and included 72 adult participants: 24 with septic shock, 24 with non-septic shock, and 24 healthy controls. Serum CitH3and procalcitonin (PCT) levels were measured using ELISA, and blood cultures were performed for septic shock patients. Median CitH3 levels were 5.58 ng/mL in healthy controls, 44.38 ng/mL in non-septic shock, and 198.7 ng/mL in septic shock patients (p < 0.001). CitH3 strongly correlated with SOFA scores (Non-septic: r = 0.793; Septic: r = 0.786) and ICU stay in septic patients (r = 0.477, p = 0.019). ROC analysis showed CitH3 performed better than PCT in distinguishing septic from non-septic shock patients (AUC 0.946 vs 0.747, p = 0.012) and from controls (AUC 0.991 vs 0.853, p = 0.017). Direct comparison also showed that CitH3 had superior predictive performance for mechanical ventilation (p = 0.038). CitH3 could be considered a reliable biomarker of septic shock. It can be regarded as a valuable tool for predicting prognosis and severity of sepsis. CitH3 could be a promising candidate for routine integration into sepsis management protocols.

Dynamic procalcitonin trajectories for prognostic prediction in wasp envenomation: A multi-center retrospective cohort study.

Procalcitonin and interleukin-6 to diagnose infection in cardiac surgery patients with hyperinflammation: a two-centre, prospective cross-sectional study.

To investigate the clinical distinctions between scrub typhus meningitis and brucellar meningitis in children, and to identify potential biomarkers with early differential diagnostic value to support clinical decision-making. A retrospective analysis was conducted on 13 pediatric patients diagnosed with brucellar meningitis admitted to Kunming Children's Hospital over the past decade. Thirteen cases of scrub typhus meningitis were selected as controls using an age- and sex-matching strategy. The clinical manifestations, laboratory findings, and cerebrospinal fluid (CSF) characteristics were compared between the two groups. Receiver operating characteristic (ROC) curve was employed to assess the diagnostic performance and clinical utility of key biomarkers. The pre-admission fever and duration of fever were significantly shorter in the scrub typhus meningitis group. Laboratory evaluation revealed that serum ferritin, procalcitonin (PCT), C-reactive protein (CRP), and creatinine (Cr) levels were markedly higher in the scrub typhus group compared with the brucellosis group. No statistically significant differences were observed in CSF biochemical parameters. ROC analysis demonstrated that ferritin (AUC = 0.870) and PCT (AUC = 0.846) exhibited the greatest diagnostic accuracy, followed by CRP (AUC = 0.814) and Cr (AUC = 0.799). All patients achieved complete clinical recovery following standardized treatment, with no recurrences or fatalities. Although scrub typhus meningitis and brucellar meningitis share considerable clinical overlap in children, serum ferritin and PCT levels may represent potential diagnostic signals for early differential diagnosis, warranting validation in larger prospective cohorts. High Ferritin levels or PCT levels may provide preliminary clues toward scrub typhus meningitis. Early recognition and targeted antimicrobial therapy are associated with favorable prognostic outcomes.

Interferon-γ (IFNγ), a double-edge sword that affects prognoses in critically ill patients: A prospective study.

Plug-in paper biosensors for the rapid detection of multiple sepsis biomarkers in blood at the emergency department.

This study aimed to analyze the clinical features ofChlamydia psittaci (C. psittaci)pneumonia and identify risk factors for severe patients to facilitate early diagnosis and treatment. In this retrospective analysis, we collected and summarized the clinical data of 57 patients withC. psittacipneumonia confirmed by metagenomic next-generation sequencing (mNGS) or targeted next-generation sequencing (tNGS), who were admitted to the First Affiliated Hospital of Guilin Medical University between July 2020 and August 2025. Patients were further divided into a severe group (n=23) and a non-severe group (n=34) for comparative analysis of their clinical characteristics. The mean age of the patients was 58.68 ± 12.36 years. Common symptoms included fever, cough/sputum, fatigue, dyspnea, and neurological and gastrointestinal symptoms. The severe group had a significantly higher incidence of fatigue, dyspnea, and neurological and gastrointestinal manifestations. Laboratory findings revealed that most patients had normal or mildly elevated white blood cell counts with lymphopenia, alongside significantly elevated levels of C-reactive protein (CRP), procalcitonin (PCT), and erythrocyte sedimentation rate (ESR). Anemia, hypoalbuminemia, and abnormalities in liver enzymes, myocardial enzymes, and electrolytes were also commonly observed. The predominant chest computed tomography finding was consolidation, with pleural effusion present in 59.6% of all patients and occurring more frequently in the severe group. Multivariate analysis identifiedCRP as an independent risk factorfor severeC. psittacipneumonia, whilealbumin and platelet count were protective factors. Pneumonia patients presenting with non-specific influenza-like symptoms should raise clinical suspicion forC. psittacipneumonia. Particular vigilance for potential progression to severe disease is warranted in male patients, the elderly, those with underlying comorbidities, and individuals presenting with neurological or gastrointestinal symptoms. Elevated CRP, hypoalbuminemia, and thrombocytopenia serve as significant predictors of severe C. psittaci pneumonia.

Procalcitonin (PCT) is an acute-phase protein and widely used marker for diagnosing bacterial infection and sepsis, but its physiological role remains incompletely defined. Interleukin-1β (IL-1β) is a critical mediator of the immune response to infection, whose excessive release can drive remote organ injury and dysfunction. Its secretion is therefore tightly controlled. Because other acute-phase proteins have been shown to regulate IL-1β secretion, we investigated whether PCT exerts a similar immunomodulatory effect and whether this influences sepsis severity, particularly in Gram-negative urosepsis. Primary human mononuclear leukocytes were stimulated to induce IL-1β release in the presence or absence of increasing PCT concentrations. In parallel, peak PCT levels, infection source, and causative pathogen were analyzed retrospectively in uroseptic patients in comparison to other septic sources, and related to Sepsis-related Organ Failure Assessment (SOFA) scores and serum lactate concentrations. PCT significantly inhibited IL-1β secretion from primary mononuclear leukocytes across the 2.5-75µg/L concentration range. Clinically, the highest PCT peaks occurred in patients with Gram-negative urosepsis. Among these, those with peak PCT values within 2.5-75µg/L had significantly lower SOFA scores and lactate levels-established indicators of sepsis severity and prognosis-compared with patients outside this range. Within a defined concentration range, PCT down-regulates IL-1β secretion and is associated with reduced markers of disease severity in Gram-negative urosepsis, compared to other sepsis entities. These findings suggest that pronounced PCT elevations in this setting may represent a protective host response rather than a worse prognosis, pointing to a novel immunomodulatory role of PCT in urosepsis that warrants further investigation. DRKS00037950, retrospectively registered on 22 September 2025.

BACKGROUNDEffective predictive indicators for clinical outcomes in septic patients with gastrointestinal dysfunction (GID) remain lacking.AIMTo evaluate the relationship between serum inflammatory biomarkers (SIBs) and clinical outcomes in patients with sepsis-induced GID.METHODSA total of 117 sepsis-induced GID patients were selected (January 2021 to January 2025). They were grouped into poor [n = 76; Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 10] and good (n = 41; APACHE II ≤ 10) prognosis groups based on outcomes. Clinical variables (sex, age, body mass index, smoking history, diabetes, hypertension, and infection site) were collected. SIBs, encompassing procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6/10, and tumor necrosis factor (TNF)-α, were analyzed. Correlation analyses were conducted to assess the associations of SIBs with Sequential Organ Failure Assessment (SOFA) and APACHE II scores. Receiver operating characteristic curves visualized SIBs’ predictive performance, and multivariate analysis identified independent outcome predictors.RESULTSThe groups were similar in age, sex, body mass index, comorbidities, and major infection site. The poor prognosis group exhibited elevated APACHE II, SOFA, PCT, CRP, IL-6, IL-10, and TNF-α than the good prognosis cohort. SIBs correlated positively with both APACHE II and SOFA scores. When used to predict outcomes individually, SIBs yielded an area under the curve range of 0.660-0.780 in septic patients with GID, whereas combined biomarker analysis increased the area under the curve to 0.906. APACHE II, SOFA, PCT, CRP, IL-6, and TNF-α acted as independent predictors of prognosis.CONCLUSIONSIBs correlate intimately with clinical outcomes in sepsis-induced GID patients.

Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with cirrhosis and ascites. This study aimed to evaluate the diagnostic performance of biomarkers-calprotectin (serum, ascitic, fecal) and serum procalcitonin (PCT)-for SBP. This prospective diagnostic accuracy study, enrolled 137 consecutive patients with cirrhosis and ascites at a tertiary care center in India. Participants were categorized into SBP (n = 55) and non-SBP (n = 82) groups based on the reference standard of ascitic fluid neutrophil count. Serum, ascitic fluid, and fecal calprotectin were measured by enzyme-linked immunosorbent assay, and serum PCT was measured by electrochemiluminescence immunoassay. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUROC). Mortality was assessed at 3 months. Patients in the SBP group had significantly higher median levels of serum PCT (0.95 μg/L vs. 0.46 μg/L; P = 0.001) and fecal calprotectin (50.00 μg/g vs. 20.00 μg/g; P < 0.001) compared to the non-SBP group. Fecal calprotectin demonstrated excellent diagnostic accuracy for SBP with an AUROC of 0.857 (95% confidence interval [CI]: 0.785-0.929), followed by serum PCT with an AUROC of 0.662 (95% CI: 0.565-0.759). An optimal cut-off of >33 μg/g for fecal calprotectin and >0.83 μg/L for serum PCT were identified. A predictive model incorporating serum PCT and fecal calprotectin achieved an AUROC of 0.862 (95% CI: 0.792-0.932). Three-month mortality was higher in the SBP group, though not statistically significant (41.5% vs. 32.1%; P = 0.276). Fecal calprotectin and serum PCT are promising, readily measurable biomarkers for the diagnosis of SBP in patients with cirrhosis.

Objectives: Procalcitonin (PCT) is used increasingly in emergency settings to guide evaluation of febrile illnesses, but its role in pediatric infectious diarrhea, particularly as a marker of severity, remains unclear. The study objective evaluates whether PCT correlates with clinical severity and outcomes in pediatric infectious diarrhea presenting to the emergency department (ED). Methods: This prospective study enrolled 105 children with infectious diarrhea presenting to a tertiary pediatric ED. Serum PCT, C-reactive protein, clinical features, hydration status, treatment decisions (including hospitalization and antibiotic use), and outcomes were analyzed. PCT cutoffs (<0.25, <0.5, and <1.0 ng/mL) were evaluated for their associations with Salmonella infection and severity measures, including dehydration, hospitalization, length of stay, and antibiotic use. Results: Thirty-five patients (33.3%) had Salmonella enteritidis. PCT levels did not differ significantly between Salmonella-positive and negative cases (median 0.49 vs. 0.46 ng/mL; p = 0.84), and PCT demonstrated poor diagnostic performance (AUC 0.49). In contrast, PCT was strongly associated with markers of severity. Compared with lower PCT levels, children with PCT ≥ 0.25 ng/mL were more frequently hospitalized (92.1% vs. 52.6%; p < 0.001) and had longer hospital stays (4.41 vs. 3.00 days; p < 0.001). Higher PCT levels were also associated with more dehydration, higher CRP (all p < 0.001), and greater antibiotic use (66.7% vs. 23.7%; p < 0.001). PCT thresholds of 0.25-0.5 ng/mL consistently identified children at increased risk for admission and higher treatment intensity. Conclusions: PCT should not be used as a diagnostic marker for Salmonella enteritidis. Instead, it reflects the host inflammatory response and is strongly associated with clinical severity in children with acute infectious diarrhea evaluated in the ED. The incorporation of PCT thresholds into ED assessment may support early severity-based risk stratification and inform decisions regarding admission and treatment intensity.

Mechanically ventilated patients are often confronted with ventilator-associated pneumonia (VAP), showing an increased risk of mortality. Early identification of biomarkers associated with VAP may ease the diagnosis and guide preventive interventions. In this study, we investigated the diagnostic value of VAP using serum and bronchoalveolar lavage fluid (BALF) levels of presepsin, procalcitonin (PCT), and lipopolysaccharide-binding protein (LBP). The serum and BALF samples were collected from 300 consecutive mechanically ventilated patients with a clinical suspicion of VAP by bronchoscopy. Among these 300 patients, 126 patients had confirmed VAP, while 174 did not meet the criteria for VAP. The reference ranges of serum presepsin, PCT, and LBP in patients with confirmed VAP were all higher than those in patients with VAP criteria not fulfilled (p < 0.0001). The reference ranges of BALF presepsin and LBP were both higher in patients with confirmed VAP than those in patients with VAP criteria not fulfilled (p < 0.0001), whereas the reference range of BALF PCT did not differ between the two groups (p = 0.202). Subgroup analysis based on main pathologies found higher levels of serum LBP, BALF presepsin, and LBP in the gram-negative group than in the gram-positive group (p < 0.001). Serum levels of presepsin, PCT, and LBP for VAP diagnosis presented AUC values of 0.81, 0.76, and 0.78, respectively. Combined analysis of serum presepsin and LBP for the diagnostic evaluation of VAP showed an AUC of 0.88, and combined analysis of the three serum levels for the diagnostic evaluation of VAP showed an AUC of 0.90. The BALF levels of presepsin and LBP for VAP diagnosis presented AUC values of 0.85 and 0.84, respectively. Combined analysis of the two BALF levels for the diagnostic evaluation of VAP showed an AUC of 0.92. Combining BALF levels of presepsin and LBP may yield better diagnostic value for the development of VAP in mechanically ventilated patients than serum. Our findings point to the importance of selecting the correct biological fluid when analyzing molecular diagnostics for definitive VAP among mechanically ventilated patients with suspicion of VAP.

Calcitonin (CT) is the established biomarker for medullary thyroid carcinoma (MTC), but its measurement is hampered by analytical limitations. Procalcitonin (PCT) and pro-gastrin-releasing peptide (ProGRP) have been proposed as alternative or complementary markers, yet the diagnostic value of ProGRP remains uncertain. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of ProGRP for MTC and compare its performance withCT. This study followed PRISMA-DTA and SEDATE guidelines. PubMed, Embase, Cochrane Library, and Open Grey were searched through June 2025 without language or date restrictions. Eligible studies assessed serum ProGRP for diagnosis or follow-up of MTC and reported or allowed reconstruction of 2×2 contingency data. Two reviewers independently screened, extracted data, and assessed study quality using QUADAS-2. A Bayesian bivariate random-effects meta-analysis estimated pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios. Comparative analyses were performed for ProGRP studies also reportingCT. Eight studies (n=4,080) were included; four reported both ProGRP and CT (n=1,064). ProGRP showed pooled sensitivity of 74 % and specificity of 95 % (AUC 0.82), while CT achieved 94 % sensitivity and 91 % specificity (AUC 0.89). Subgroup analyses confirmed consistent ProGRP performance across diagnostic and follow-up settings. No publication bias was observed. ProGRP demonstrates high specificity but lower sensitivity than CT for MTC diagnosis and surveillance. Although not a replacement for CT, ProGRP may serve as a valuable complementary biomarker, particularly in inconclusive cases. Harmonization of assays and prospective validation are required to define universal thresholds and integrate ProGRP into multimarker diagnostic algorithms.

We assessed baseline C-reactive protein (CRP) and procalcitonin levels in asymptomatic individuals from malaria-endemic West Africa. C-reactive protein remained unaffected by Plasmodium falciparum parasitemia, while procalcitonin (PCT) was more frequently detectable among malaria-positive individuals. These findings support that CRP thresholds remain valid and highlight the need to explore parasite density-PCT associations.

ObjectiveThis study aims to investigate the efficacy of enteral nutrition support combined with prone position mechanical ventilation in patients with severe pneumonia.MethodsThis retrospective cohort study included 55 patients with severe pneumonia, who were allocated to a control group (n = 35) receiving conventional mechanical ventilation combined with early enteral nutrition support, and an observation group (n = 20) receiving prone position mechanical ventilation combined with early enteral nutrition support. The intervention lasted for 1 week. Changes in blood gas indicators were compared before and after the intervention. Improvement in nutritional status and inflammatory indicators, including serum prealbumin (PAB), albumin (ALB), haemoglobin (HGB) and C-reactive protein (CRP), and procalcitonin (PCT), were assessed. The incidence of adverse events during the intervention was compared between groups. This study was approved by the Ethics Review Committee of our hospital, and written informed consent was obtained from all participants.ResultsAfter the intervention, both groups showed increased PaO2, SpO2, and PaO2/FiO2 levels and decreased PaCO2 levels, with more pronounced improvement observed in the observation group. Nutritional indicators (PAB, ALB, and HGB) improved in the observation group. CRP and PCT levels were reduced in both groups, with the observation group demonstrating lower levels. The observation group showed a lower incidence of adverse events than the control group (15.00% vs. 42.86%).ConclusionEnteral nutrition support combined with prone position mechanical ventilation reduces the incidence of adverse events, improves respiratory function and nutritional status, and alleviates inflammatory response in patients with severe pneumonia.